YY1 coopère avec AP-2 pour stimuler l'expression du gène ERBB2 dans les cellules de cancer du sein

peer reviewedOverexpression of the ERBB2 oncogene is observed in about 30% of breast cancers and is generally correlated with a poor prognosis. Previous results from our and other laboratories indicated that elevated transcriptional activity contributes significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell lines. Activator protein 2 (AP-2) transcription factors account for this overexpression through two recognition sequences located 215 and 500 bp upstream from the transcription start site. Furthermore, AP-2 transcription factors are highly expressed in cancer cell lines overexpressing ERBB2. In this report, we examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of ERBB2 promoter activity. We detected high levels of YY1 transcription factor in mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2alpha transcriptional activation of the ERBB2 promoter through an AP-2 site both in HepG2 and in HCT116 cells, whereas a carboxyl-terminal-truncated form of YY1 cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in chromatin immunoprecipitation assays. Our data thus provide evidence that YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites

Follicular growth and ovulation in the queen

The queen is a seasonally polyoestrus, induced ovulator. Due to the limited follicular size, clinical follow-up of terminal follicular growth is difficult in this species. In this study, ovarian ultrasonography has been performed during 9 anovulatory cycles and 12 ovulatory cycles. Follicles appeared as well-defined anechoic circular zones. Mean estrus duration was 7.4 days. On the first day of behavioural estral modifications, 4.8 ± 0.2 follicles (2-7 per female) of 2.3 ± 0.01 mm mean diameter were present on the ovaries. Follicular growth continues at a rate of 0.2 ± 0.04 mm per day. At least one follicle of the cohort reaches a diameter greater than 3.0 mm. Maximal follicular growth was reached 3.8 ± 0.3 days after the onset of estrus and the diameter of the largest follicle was 3.5 ± 0.04 mm. In the absence of ovulation, follicular diameter decreased from 0.1 ± 0.01 mm per day until the end of estrus. The first day after the end of behavioural estrus, the diameter of the largest follicle of each cohort was 2.7 ± 0.05 mm. When ovulation was mechanically induced, it began 23 to 28 hours after vaginal stimulations and lasted 10 hours. It was visualized by anechoic images disparition. No correlation has been observed between follicular development and either vaginal smear characteristics, or time spent from the onset of estrus. Ultrasonography revealed to be the more reliable technique to examine the follicular development and its main interest is the determination of the optimal time for ovulation induction before artificial insemination.La chatte est une femelle à polyoestrus saisonnier et à ovulation provoquée. Compte tenu de la faible taille des follicules, le suivi clinique de la croissance folliculaire terminale est difficile dans cette espèce. Les ovaires ont été observés au cours de 9 cycles anovulatoires et 12 cycles ovulatoires grâce à un échographe de très haute résolution. Les follicules apparaissent sous forme de zones circulaires anéchogènes bien délimitées. Les chaleurs durent en moyenne 7,4 jours. Le premier jour d'apparition des manifestations comportementales de l'œstrus, 4,8 ± 0,2 follicules (entre 2 et 7 par chatte) sont présents avec un diamètre moyen de 2,3 ± 0,01 mm. La croissance des follicules se poursuit ensuite à raison de 0,2 ± 0,04 mm par jour. Au moins un follicule de la cohorte atteint un diamètre supérieur à 3 mm. La croissance folliculaire maximale est atteinte 3,8 ± 0,3 jours en moyenne après le début des chaleurs; le diamètre du plus gros follicule est de 3,5 ± 0,04 mm. En l'absence d'ovulation, le diamètre folliculaire diminue d'en moyenne 0,1 ± 0,01 mm par jour jusqu'à la fin des chaleurs. Le premier jour d'arrêt des manifestations comportementales, le diamètre du plus gros follicule de chaque cohorte est de 2,7 ± 0,05 mm. Lorsqu'elle est induite par stimulation vaginale, l'ovulation débute 23 à 28 heures après la première stimulation et s'étale sur environ 10 heures. Elle se traduit par la disparition des images anéchogènes. Cette étude montre que le stade de croissance folliculaire ne peut être relié ni aux caractéristiques du frottis vaginal ni à la durée écoulée depuis le début des manifestations comportementales. L'échographie semble être la technique la plus fiable pour déterminer le stade de croissance folliculaire et donc décider du moment optimal d'induction de l'ovulation en vue de l'insémination

Porcine neurofibromatosis : a new syndrome

A genetically dominant neoplasic disease similar to human neurofibromatosis has just been discovered in pigs. Two of the three clinical forms known in man have been identified in several pig farms: one with large subcutaneous tumours, the other exclusively intradermal. Clinical and pathology studies have been performed on these lesions. Tumour cells are being cultured and the sequencing of their genome is underway. This research is especially important because no animal model of this very common disease in man was available until now.Une affection tumorale similaire à la neurofibromatose de l'Homme vient d'être découverte chez le porc. Cette maladie, de caractère génétique dominant, a été retrouvée dans plusieurs élevages sous deux des trois formes rencontrées chez l'Homme, l'une à grosses tumeurs sous-cutanées et l'autre, strictement intradermique. Ces lésions ont été étudiées aux plans clinique et anatomopathologique. Les cellules tumorales ont été mises en culture et le séquençage de leur génome entrepris. Ce travail revêt une importance toute particulière car il n'existait jusqu'alors aucun modèle animal de cette maladie très fréquente chez l'Homme

The combined immunodetection of AP-2α and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors

INTRODUCTION: Overexpression of the ERBB2 oncogene is observed in about 20% of human breast tumors and is the consequence of increased transcription rates frequently associated with gene amplification. Several studies have shown a link between activator protein 2 (AP-2) transcription factors and ERBB2 gene expression in breast cancer cell lines. Moreover, the Yin Yang 1 (YY1) transcription factor has been shown to stimulate AP-2 transcriptional activity on the ERBB2 promoter in vitro. In this report, we examined the relationships between ERBB2, AP-2alpha, and YY1 both in breast cancer tissue specimens and in a mammary cancer cell line. METHODS: ERBB2, AP-2alpha, and YY1 protein levels were analyzed by immunohistochemistry in a panel of 55 primary breast tumors. ERBB2 gene amplification status was determined by fluorescent in situ hybridization. Correlations were evaluated by a chi2 test at a p value of less than 0.05. The functional role of AP-2alpha and YY1 on ERBB2 gene expression was analyzed by small interfering RNA (siRNA) transfection in the BT-474 mammary cancer cell line followed by real-time reverse transcription-polymerase chain reaction and Western blotting. RESULTS: We observed a statistically significant correlation between ERBB2 and AP-2alpha levels in the tumors (p < 0.01). Moreover, associations were found between ERBB2 protein level and the combined high expression of AP-2alpha and YY1 (p < 0.02) as well as between the expression of AP-2alpha and YY1 (p < 0.001). Furthermore, the levels of both AP-2alpha and YY1 proteins were inversely correlated to ERBB2 gene amplification status in the tumors (p < 0.01). Transfection of siRNAs targeting AP-2alpha and AP-2gamma mRNAs in the BT-474 breast cancer cell line repressed the expression of the endogenous ERBB2 gene at both the mRNA and protein levels. Moreover, the additional transfection of an siRNA directed against the YY1 transcript further reduced the ERBB2 protein level, suggesting that AP-2 and YY1 transcription factors cooperate to stimulate the transcription of the ERBB2 gene. CONCLUSION: This study highlights the role of both AP-2alpha and YY1 transcription factors in ERBB2 oncogene overexpression in breast tumors. Our results also suggest that high ERBB2 expression may result either from gene amplification or from increased transcription factor levels

The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC). METHODS: We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. RESULTS: EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. CONCLUSIONS: These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.Peer reviewe

Impact of Baricitinib on Patients’ Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients’ lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well

Using Dynamic Stochastic Modelling to Estimate Population Risk Factors in Infectious Disease: The Example of FIV in 15 Cat Populations

BACKGROUND:In natural cat populations, Feline Immunodeficiency Virus (FIV) is transmitted through bites between individuals. Factors such as the density of cats within the population or the sex-ratio can have potentially strong effects on the frequency of fight between individuals and hence appear as important population risk factors for FIV. METHODOLOGY/PRINCIPAL FINDINGS:To study such population risk factors, we present data on FIV prevalence in 15 cat populations in northeastern France. We investigate five key social factors of cat populations; the density of cats, the sex-ratio, the number of males and the mean age of males and females within the population. We overcome the problem of dependence in the infective status data using sexually-structured dynamic stochastic models. Only the age of males and females had an effect (p = 0.043 and p = 0.02, respectively) on the male-to-female transmission rate. Due to multiple tests, it is even likely that these effects are, in reality, not significant. Finally we show that, in our study area, the data can be explained by a very simple model that does not invoke any risk factor. CONCLUSION:Our conclusion is that, in host-parasite systems in general, fluctuations due to stochasticity in the transmission process are naturally very large and may alone explain a larger part of the variability in observed disease prevalence between populations than previously expected. Finally, we determined confidence intervals for the simple model parameters that can be used to further aid in management of the disease

Anatomie radiographique des lagomorphes, rongeurs et furets de compagnie, réalisation sur un support informatique d'une banque d'images radiographiques

Nous avons anesthésié des représentants sains de 7 espèces de mammifères afin de réaliser des clichés de référence du thorax, de l abdomen, du squelette axial et appendiculaire. Ces clichés ont ensuite été scannés puis légendés avec le logiciel Adobe Photoshop® CS. Les images sont alors présentées sur un support informatique afin d en permettre l accès au plus grand nombre : nous avons créé le site Radio NAC sur le réseau intranet de l école vétérinaire d Alfort à l aide du logiciel Dreamweaver® MX.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF

CREATION DE BANQUES D'IMAGES RADIOGRAPHIQUES COMMENTEES DE LESIONS DU SQUELETTE APPENDICULAIRE DES CARNIVORES DOMESTIQUES SUR SUPPORT INFORMATIQUE (accès réservé)

Une banque d'images radiographiques commentées de lésions du squelette appendiculaire des Carnivores domestiques a été réalisée pour faciliter l'enseignement. Des cas radiographiques intéressants ont été recherchés dans les archives de l'ENVA de ces quinze dernières années. Ces radiographies sélectionnées ont été scannées, annotées de manière explicative et les compte-rendus revus, tapés afin de monter un site informatique, consultable sur le réseau Intranet de l'Ecole Nationale Vétérinaire d'Alfort. Ce support informatique permet une diffusion aisée à plus long terme aux Ecoles Vétérinaires françaises ou même étrangères et aux praticiens sur le réseau Internet, ainsi que la mise en place d'une radiothèque interactive et réactualisable.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF